Subsequent studies have helped to clarify the role of diacetyl in substance toxicity. Toxicology studies have shown that vapors from heated butter flavorings can cause damage to airways in animals (Hubbs et al. 2002external icon). Studies in both rats and mice demonstrate that the cells lining the airways can be damaged by inhaling diacetyl vapors as a single agent exposure in both acute and sub-chronic studies (Hubbs et al. 2008external icon, Morgan et al. 2008external icon). In mice, aspiration of diacetyl alone caused a pattern of injury that replicates some of the features of human obliterative bronchiolitis (Morgan et al. 2008external icon). In addition, inhaling either diacetyl or the related flavoring, 2,3-pentanedione can cause an obliterative bronchiolitis-like condition in rats (Morgan et al. 2016external icon).
Furthermore, diacetyl reacts with proteins and a recent study demonstrating striking changes in protein homeostasis in the airways of diacetyl-exposed mice strongly implicates protein damage in airway epithelium as the mechanism for diacetyl-induced airway injury (Hubbs et al. 2016external icon). Dosimetry studies indicate that at a given exposure concentration, a much greater concentration of diacetyl can reach the deep lung of humans than reaches the deep lung of rats (Gloede et al. 2011external icon, Morris and Hubbs. 2009external icon). These findings support the hypothesis that diacetyl vapors are an inhalation hazard in the workplace. Also, chemical workers in a plant that manufactured diacetyl and coffee workers exposed to diacetyl developed the same type of lung disease as microwave popcorn workers (van Rooy et al. 2007 and 2009). The chemical workers had less complicated exposures than microwave popcorn workers. Overall, current evidence points to diacetyl as one agent that can cause flavorings-related lung disease.
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The alpha-diketone, 2,3-pentanedione, has received attention as a flavoring substitute for diacetyl. It is also known as acetyl propionyl or by CAS number 600-14-6. It is structurally very similar to diacetyl since 2,3-pentanedione is a 5-carbon alpha-diketone and diacetyl is a 4-carbon alpha-diketone. Recent mechanistic studies implicate the alpha-diketone functional group in the airway toxicity of diacetyl (Morgan et al. 2016external icon, Hubbs et al. 2016external icon).
Reports of 2,3-pentanedione toxicity were first published in 2010 (Hubbs et al. 2010aexternal icon, Morgan et al. 2010). A follow-up full length publication demonstrated that acute inhalation exposures to 2,3-pentanedione cause airway epithelial damage that is similar to diacetyl in laboratory studies (Hubbs et al. 2012external icon). In longer 2-week inhalation studies in rats, researchers from the National Institute of Environmental Health Sciences (NIEHS) found that repeated exposures to either 2,3-pentanedione or diacetyl can cause airway fibrosis, including obliterative bronchiolitis-like changes, in rats (Morgan et al. 2016external icon). In the acute inhalation study of 2,3-pentanedione, changes in gene expression were noted in the brain (Hubbs et al. 2012external icon). Similarly, diacetyl can cause changes in gene expression and other markers of damage in the olfactory bulb of the mouse brain (Hubbs et al. 2016external icon).
As a group, these publications raise concerns that the toxicologic effects of diacetyl may be shared with close structural analogs used in food manufacturing such as 2,3-hexanedione and 2,3-heptanedione (Day et al. 2011external icon). The 6-carbon alpha-diketone, 2,3-hexanedione is less chemically reactive than diacetyl or 2,3-pentanedione, and only 2 of 12 rats had bronchial fibrosis after a 2-week inhalation exposure to 2,3-hexanedione (Morgan et al. 2016external icon).
Hubbs, A.F., Fluharty, K.L., Edwards, R.J., Barnabei, J.L., Grantham, J.T., Palmer, S.M., Kelly, F., Sargent, L.M., Reynolds, S.H., Mercer, R.R., Goravanahally, M.P., Kashon, M.L., Honaker, J.C., Jackson, M.C., Cumpston, A.M., Goldsmith, W.T., McKinney, W., Fedan, J.S., Battelli, L.A., Munro, T., Bucklew-Moyers, W., McKinstry, K., Schwegler-Berry, D., Friend, S., Knepp, A.K., Smith, S.L. and Sriram, K. [2016]. Accumulation of Ubiquitin and Sequestosome-1 Implicate Protein Damage in Diacetyl-Induced Cytotoxicity. The American journal of pathology, 186, 2887-2908.
Morgan, D.L., Jokinen, M.P., Johnson, C.L., Price, H.C., Gwinn, W.M., Bousquet, R.W. and Flake, G.P. [2016]. Chemical Reactivity and Respiratory Toxicity of the alpha-Diketone Flavoring Agents: 2,3-Butanedione, 2,3-Pentanedione, and 2,3-Hexanedione. Toxicol Pathol, 44, 763-783.
> For Garlic Chipotle Marinade: In a blender, puree garlic, onion, beer, olive oil and black pepper. Transfer puree to large mixing bowl and add Tabasco Chipotle Sauce and salt, as desired. Marinate steak in mixture for at least six hours.
>For Sweet Chipotle Marinade: In a blender, puree garlic, red bell pepper, onion, cinnamon, paprika, olive oil, agave syrup, lime juice, orange juice, water, chipotle sauce and salt, then divide marinade over chicken and shrimp in separate sealed plastic bags. Allow shrimp to marinate in mixture for eight hours and chicken breasts for 24 hours.
Road salt dissolves and flushes away into surface water, so high salt concentrations are often found in rivers and streams after a significant amount of snow has melted. But les could be used with proper training.
Something about our medieval past continues to fascinate contemporary readers, including a readership most often associated with all that is shiny and new: children and young adults. For this panel, which will be proposed for the 2016 Texas Medieval Association (TEMA) conference, we seek papers that focus on the medieval in texts for young audiences. Some possible areas for exploration include:
Transformations of literary textuality and reading practices on small electronic devices; theoretical approaches from areas such as multimodality, narratology, semiotics, reception, authorship, and screen interface. 300 word abstract, brief bio by 15 March 2016; Ellen McCracken (emccr@spanport.ucsb.edu).
The Society of Akron Graduate English Scholars is pleased to announce a call for papers for its upcoming interdisciplinary conference on April 28, 2016. We welcome creative writers and scholars from various disciplines to discuss the theme, "Hysteria." This free conference is open to both undergraduate and graduate students. We invite scholarship and reflection addressing one or more elements of hysteria and its historical and cultural context.
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